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K. Narfstrom, K. Holland Deckman, V. David, S. O'Brien, M. Menotti-Raymond; Mutation Discovered in a Feline Model for Early Onset Severe Retinal Blinding Disease. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3741.
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© ARVO (1962-2015); The Authors (2016-present)
To elucidate the gene defect in a pedigree of mixed breed shorthaired cats segregating for autosomal dominant photoreceptor dysplasia (rdy), a disease previously characterized clinically and morphologically in Abyssinian cats, comparable to early onset Retinitis Pigmentosa, (RP) and Leber Congenital Amaurosis (LCA).
Affected cats were crossed with unrelated normal cats producing a pedigree with 9 normal and 10 affected offspring, phenotyped by clinical ophthalmic examinations using ophthalmoscopy and full-field electroretinography at age 6-8 weeks. Linkage analysis was performed in the 26 member pedigree using microsatellites tightly linked to 17 candidate genes or genomic regions previously characterized and reported to be mutated in dominantly inherited retinal degenerations in humans or animal models.
Significant linkage was established to a microsatellite in a genomic region adjacent to the candidate gene CRX (LOD= 5.56, θ = 0) on cat chromosome E2, 98.8 Mb. Additional microsatellites developed from the 2X cat whole genome sequence supported linkage of rdy to the CRX gene. DNA sequence analysis of genomic DNA and cDNA generated from retinal tissue from affected and unaffected individuals identified a single base pair deletion in the 3’-region of CRX in affected individuals. The deletion introduces a frame-shift in the transcript, and a subsequent premature stop codon, which would truncate the putative CRX peptide.
It has been demonstrated previously that the CRX gene is critical in retinal development and implicated in human early onset retinal degenerations. Deletions/mutations in the 3’ end of CRX are reported as causative of human RP and LCA. The rdy mutant cat offers promise as a valuable animal model for human congenital retinal blinding disease.
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